Identification and characterization of yeast SNF1 kinase homologs in Leishmania major.

IF 3.9 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Frontiers in Molecular Biosciences Pub Date : 2025-03-24 eCollection Date: 2025-01-01 DOI:10.3389/fmolb.2025.1567703

Gaurav Shoeran, Namrata Anand, Upninder Kaur, Kapil Goyal, Rakesh Sehgal

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引用次数: 0

Abstract

Background: Sucrose Non Fermenting1 (SNF1) constitutes a family of protein kinases conserved in eukaryotes, plants, and fungi. SNF1 has been known to play a crucial role in stress adaptation and metabolism, enabling organisms to respond to changing environmental conditions. Initially identified in yeast, SNF1 is essential for shifting from the primary carbon source, glucose, to secondary carbon sources like sucrose. Homologs of this protein family were identified in Leishmania major, a protozoan parasite and we aimed to determine their role in this parasite.

Methods: In the present study, we identified the putative homologs of SNF1 kinase in L. major and knock out strains were prepared using the CRISPR-Cas9 knock-out strategy. The developed strains were evaluated for their growth, characteristics, protein expression and ultra structural changes in vitro and virulence in a mouse model.

Results: One of the strain named N2, was found to be completely avirulent and showed limited growth, lack of glycosomes and had a fewer mitochondria with deformed cristae. The N2 strain failed to produce infection in mice when compared to WT mice. Proteome analysis revealed an increase in ribosomal proteins in the N2 strain, highlighting the role of ribosomes in stress adaptation.

Conclusion: The essentiality of this gene for developing infections in mice underscores its potential in the development of future antileishmanial therapies and live attenuated strains.

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来源期刊

Frontiers in Molecular Biosciences Biochemistry, Genetics and Molecular Biology-Biochemistry

CiteScore

7.20

自引率

4.00%

发文量

1361

审稿时长

14 weeks

期刊介绍： Much of contemporary investigation in the life sciences is devoted to the molecular-scale understanding of the relationships between genes and the environment — in particular, dynamic alterations in the levels, modifications, and interactions of cellular effectors, including proteins. Frontiers in Molecular Biosciences offers an international publication platform for basic as well as applied research; we encourage contributions spanning both established and emerging areas of biology. To this end, the journal draws from empirical disciplines such as structural biology, enzymology, biochemistry, and biophysics, capitalizing as well on the technological advancements that have enabled metabolomics and proteomics measurements in massively parallel throughput, and the development of robust and innovative computational biology strategies. We also recognize influences from medicine and technology, welcoming studies in molecular genetics, molecular diagnostics and therapeutics, and nanotechnology. Our ultimate objective is the comprehensive illustration of the molecular mechanisms regulating proteins, nucleic acids, carbohydrates, lipids, and small metabolites in organisms across all branches of life. In addition to interesting new findings, techniques, and applications, Frontiers in Molecular Biosciences will consider new testable hypotheses to inspire different perspectives and stimulate scientific dialogue. The integration of in silico, in vitro, and in vivo approaches will benefit endeavors across all domains of the life sciences.